摘要：SummaryHow the noisy expression of regulatory proteins affects timing of intracellular events is an intriguing fundamental problem that influences diverse cellular processes. Here we use the bacteriophage λ to study event timing in individual cells where cell lysis is the result of expression and accumulation of a single protein (holin) in theEscherichia colicell membrane up to a critical threshold level. Site-directed mutagenesis of the holin gene generated phage variants that vary in their lysis times from 30 to 190 min. Observation of the lysis times of single cells reveals an intriguing finding—the noise in lysis timing first decreases with increasing lysis time to reach a minimum and then sharply increases at longer lysis times. A mathematical model with stochastic expression of holin together with dilution from cell growth was sufficient to explain the non-monotonic noise profile and identify holin accumulation thresholds that generate precision in lysis timing.Graphical AbstractDisplay OmittedHighlights•Mutations in timekeeper protein alter event timing and noise in event timing•Data show noise in event timings follow a concave up shape with increasing threshold•Mathematical modeling identifies optimal threshold minimizing noise in event timing•Results imply that noise in event timing can be a target of natural selectionBiological Sciences; Cell Biology; In Silico Biology
